MXPA01001093A - Compound and method for the prevention and/or the treatment of allergy. - Google Patents

Abstract

The present invention is related to a compound for the prevention and/or the treatment of allergy consisting of: at least one allergen antigenic determinant which is recognised by a B cell or an antibody secreted by a B cell of a non-atopic individual to said allergen, and at least one antigenic determinant of an antigen different from said allergen which triggers T cell activation.

Description

COMPOSITE AND PROCEDURE FOR THE PREVENTION AND / OR TREATMENT OF ALLERGY PAMPO OS THE INVENTION The present invention relates to a new compound and to a new process for the prevention and / or treatment of allergy and / or diseases of allergic origin, particularly the allergy of immediate hypersensitivity.

BACKGROUND OF THE INVENTION Immediate hypersensitivity is a form of allergic reaction that develops very quickly, ie after a few seconds or minutes of exposure of the patient to the allergen that causes it. Such an immediate reaction may be followed by a second delayed-onset reaction that can lead to inflammatory changes in the target organ and is manifested by chronic symptoms, such as asthma or atopic dermatitis. The immediate hypersensitivity is mediated by antibodies that belong mainly, but not exclusively, to the IgE isotype. IgE antibodies bind to specific receptors in cells such as basophils, mast cells or Langerhans cells. In an exposure to allergens, the IgE bound to the surface transduces a signal in the cell, which is followed by an activation of the cell, which in the case of basophils and mast cells is accompanied by the release of preformed mediators, such as histamine and enzymes, and the synthesis of arachidonic acid metabolites. These mediators are responsible for the development of allergic signs and symptoms, such as bronchospasm, vasodilation, mucus hypersecretion and stimulation of sensory nerve endings that result in itching. IgE antibodies are produced by B-cells that received appropriate activation signals. A complete description of the mechanisms by which IgE antibodies are produced can be found in appropriate journals (see for example Vercelli D., Allergy Proc. 14, pages 413-416 (1993)). The current treatment of allergic symptoms includes allergen avoidance, drug treatment and immunotherapy. The complete avoidance of exposure to allergens is the most logical method, but it is very difficult, or impossible to achieve in the vast majority of cases. Drug therapy is useful, but relieves symptoms without influencing its causes.

In addition, a drug treatment is usually limited by undesirable side effects. Current methods for immunotherapy are: 1) a conventional hyposensitization which is a treatment consisting in administering to the patient progressively increasing doses of the allergen (s) against which it has developed a sensitivity; 2) a modification of the allergens that is aimed at reducing their recognition by specific antibodies, IgE in particular; 3) the use of peptides derived from allergens to interfere in an affine interaction between specific B and T cells or that contain a B cell epitope that binds to IgE. In patent application WO93 / 08279 said allergen-derived peptides containing one or a few T cell epitopes used in experiments in animals and humans are described in an attempt to inhibit the activation of specific T cells and induce a state of inability of T cell response. A human application of said concept consists in the administration of a peptide derived from the sequence of T cell epitopes present in Fel di allergen, by subcutaneous injections in cat sensitive individuals (Wallner BP, Gefter ML, Allergy 49, pages 302-308 (1994)). An alternative complementary method of this concept has also been used in animal experiments. The peptides used are modified in such a way that they maintain the ability to bind to MHC class II determinants in specific B cells, but have lost their ability to activate the corresponding T cells (O'Hehir R.E. et al., International Immunology 3, pages 819-826 (1991)). It is known that allergic reactions are generated by the release of mediators from target cells, such as basophils or mast cells, which present high affinity surface receptors for IgE, which are occupied by IgE antibodies. The minimum requirement for a release of mediators to occur is that two IgE molecules that recognize the same allergen crosslink, which in turn crosslink the receptor, resulting in the transduction of an activation signal within the cell. If only one molecule of IgE is able to bind to the allergen, no activation of the cell takes place, but the IgE binding site would be occupied, preventing the activation of the cell on exposure to a native allergen. It has been claimed therefore that the use of a single epitope that binds to IgE constitutes a suitable method for the treatment of allergic diseases (Ball T. ei al., J. Biol. Chem. 269, pages 28323-28328 (1994) , EP-A-0714662).

STATE OF THE ART US Patent 4,946,945 discloses a protein conjugate useful in immunotherapies, composed of a biological response modifier (BRM) and an allergen. Said conjugate could be combined with a pharmaceutically acceptable excipient. Disclosed herein are cytokine, bacterial, fungal and viral immunopotentiators and thymus hormones such as BRM suitable for use. Patent application WO95 / 31480 describes the preparation and use of a synthetic compound consisting of two alpha helices with specific arrangements of various amino acids. Said compound is used as a support for the union of functional units, especially epitopes of B and / or T. DEFINITIONS The term "atopy" is understood to mean a predisposition, partially of genetic origin, of an individual who has an immune system that produces an excess of anti-genes belonging to the IgE isotype in response to exposure to allergens. The individuals that present these characteristics are therefore called "atopic individuals". An "allergen" is defined as a substance, normally a macromolecule of protein composition, which activates the production of IgE anticuefos in predisposed individuals, preferably genetically disposed (atopic individuals). Similar definitions are presented in the following references: Clin. Exp. Allergy, No. 26, pages 494-516 (1996); Mol. Biol. Of Allergy and Immunology, compiler R. Bush, Immunology and Allergy Clinics of North American Series (August 1996). Said allergens are preferably the main allergens selected from the group consisting of: - food allergens present in peanuts, cod, egg white, soybeans, shrimps, milk and wheat, - domestic dust mite allergens obtained from of Dermatophagoides spp. pteronyssinus, farinae and microceras, Euroglyphus maynei or Blomia, - allergens from insects, present in cockroaches or hymenoptera, - allergens from pollen, especially pollens from trees, herbs and weeds, - allergens present in animals, especially in cats, dogs , horses and rodents, - allergens present in fungi, especially from Aspergillus, Alternaria or Cladosporium, and - allergens of occupational diseases present in such products as latex, amylase, etc. These allergens can also be major allergens present in molds or various drugs, such as hormones, antibiotics, enzymes, etc. The "allergy" is the set of signs and symptoms that are observed whenever an atopic individual encounters an allergen against which he has been sensitized, which can result in the development of various diseases and symptoms, such as allergic rhinitis, bronchial asthma, atopic dermatitis, etc. "Hypersensitivity" is an adverse reaction produced in a susceptible individual on exposure to an antigen against which it has become sensitive; Immediate hypersensitivity depends on the production of IgE antibodies and is therefore synonymous with allergy.

The term "epitope" or the term "antigenic determinant" means one or more portions (which may define a conformational epitope) of an antigen (structure of a macromolecule, including an allergen, preferably constituted by a protein composition but also constituted by one or more haptens or portion of a pharmaceutically active compound) that are specifically recognized and bound to an antibody or a cell surface receptor of a B or T lymphocyte.

BRIEF DESCRIPTION OF THE INVENTION The purpose of the present invention is to provide a vaccination strategy by which the antibody response produced by atopic individuals against allergens deviates from the major determinants of allergens that are spontaneously recognized by atopic individuals., to determinants in the same molecule that are spontaneously recognized by antibodies from non-atopic individuals, or to determinants that are not spontaneously recognized by most individuals, regardless of their atopic status. The present invention relates to a compound comprising either at least one antigenic determinant of allergen that is recognized by a B cell or an antibody secreted by a B cell of a non-atopic individual (to said allergen) (including a a cryptic determinant that is not recognized by atopic individuals and is minimally recognized by non-atopic individuals) and that is preferably not recognized by a T cell, and at least one antigenic determinant of an antigen different from said allergen, said antigenic determinant giving rise to T-cell activation, or - a nucleotide sequence encoding said two antigenic determinants, said sequence possibly being linked to one or more active regulatory sequences in a patient's cell. The antigenic determinants of specific allergens present in known main allergens are easily identified by the person skilled in the art, who can select said epitopes or antigenic determinants of said allergen that are recognized by non-atopic individuals (non-atopic individuals to said allergen) and who they may be different from the other epitopes for which atopic individuals produce antibodies, as described above. Similarly, the person skilled in the art can select the specific antigenic determinant of any antigen (different from said allergen which is known to give rise to the activation of T cells). Preferably, said antigen is not an allergen. In the examples that follow, a preferred selection of said epitope is described. The compound according to the present invention will produce in atopic patients a deviation of the anti-allergen immune response towards epitopes or antigenic determinants that are not spontaneously recognized or are only minimally detected by antibodies from atopic patients. In the compound according to the present invention, the antigenic determinant of allergen and the antigenic determinant of the non-allergic antigen are preferably peptide sequences chemically linked together (in the form of a linear tandem or in branched form), preferably by means of a peptide linker, which is preferably constituted by at least two amino acids. The compound according to the present invention is in a linear or cyclic form, with or without additional residues used, for example, to block peptide-peptide interactions. Advantageously, the allergen is selected from the group consisting of Der pl and Der pll of the domestic dust mite Dermatophagoides pteronyssinus, the main antigen of Aspergillus fumigatus, the staphylococcal enterotoxin B (SEB) and the bovine β-lactoglobulin or the allergen that it is described in the document Clin. Exp. Allergy, No. 26, pages 494-516 (1996); Mol. Biol. Of Allergy and Immunology, compiler R. Bush, Immunology and Allergy Clinics of the North American Series (August 1996). Advantageously, in the compound according to the present invention, the antigenic determinant of an antigen that gives rise to the activation of T cells is an epitope of T cells (preferably a helper T cell epitope) of tetanus toxoid, diphtheria, mycobacteria, antigens of the influenza virus or measles (other examples of such T-cell epitopes are described in Table II of W095 / 26365).

Preferably, the compound according to the present invention is selected from the group consisting of the peptides having the following amino acid sequences: SEC ID n ° 1: QYIKANSKFIGITELGGHEIKKVLVPGCHGS SEC ID n ° 2: HEIKKVLVPGCHGS SEC ID n ° 3: DQYIKANSKFIGITELGGQYIKANSKFIGITELSSCHGSEPCIIHRGKPFGGCHG SEPCIIHRGKPFSSCHGSEPCIIHRGKPFGGCHGSEPCIIHRGKPFSSCHGSEP CIIHRGKPFGGCHGSEPCIIHRGKPFSR SEC ID n ° 4: PKYVKQNTLKLATGKKGPKYVKQNTLKLATGKKGVIIGIK SEQ ID NO: 5: QYIKANSKFIGITELGGCHGSEPCNIHRGKPF or a nucleotide sequence encoding at least one of said amino acid sequences, preferably the nucleotide sequence SEQ ID No. 6: GAATTCCCACCATGGATCAGTATATAAAAGCAAATTCTAAATTTATAGGTAT AACTGAACTAGGAGGTTGCCATGGTTCAGAACCATGTATCATTCATCGTGG TAAACCATTCGGCGGTT- GTCACGGAAGTGAGCCTTGCATTATACACAGAGGAAAGCCGTTCTA-AGCGGCCGC. Another aspect of the present invention relates to a pharmaceutical, cosmetic, food and / or feed composition comprising the compound according to the invention and an acceptable pharmaceutical, cosmetic, food and / or animal excipient. Preferably, said pharmaceutical composition consists of a vaccine which may comprise a pharmaceutically acceptable excipient which can consist of any suitable non-toxic substance suitable for administering the composition (vaccine) according to the present invention to a patient and obtaining the desired therapeutic or prophylactic properties. The pharmaceutically acceptable excipients according to the present invention, suitable for oral administration, are those well known to the person skilled in the art, such as tablets, coated or uncoated pills, capsules, solutions or syrups. Other suitable excipients or pharmaceutical vehicles may vary according to the mode of administration (cutaneous, epicutaneous, subcutaneous, intradermal, inhalation, patch, intravenous, intramuscular, parenteral, oral, etc.). When the compound according to the present invention consists of a nucleotide sequence, the compound according to the invention can be used neat or in a pharmaceutically acceptable excipient, such as a "vector" used for the transfection, transduction and expression of said sequence by a cell of the patient (including expressing a secretion outside the cell of the peptide sequence encoded by said nucleotide sequence). Said "vector" is preferably selected from the group consisting of plasmids, viruses, (retroviruses, adenoviruses, etc.), lipid vectors (such as cationic vesicles, liposomes, etc.), molecules or devices that result in a modification chemistry or physics of the transfected cell (dextran phosphate, calcium phosphate, a microinjection device, an electroporation device, etc.) or modified recombinant organisms comprising the compound according to the present invention derived, for example, from Salmonella strains or Mycobacteria, a nucleic acid encapsulated in the form of micro- or nanoparticles, such as chitosan, as described by Roy et al., Nature Medicine 5, pages 387-391 (1999), etc. The genetic modification of the patient's cell (s) for an ex vivo or in vivo treatment can be obtained by the person skilled in the art according to the known procedures in the field of gene therapy (such as the one described). in WO91 / 02805, WO91 / 18088 and WO91 / 15501). The pharmaceutical composition or vaccine according to the present invention can also comprise adjuvants (including helper viruses) well known to the person skilled in the art, which can modulate the humoral, local, mucosal and / or cellular response of a patient's immune system and improve the use of the compound according to the present invention. Adjuvants can be found in different forms, as long as they are suitable for administration to humans. Examples of such adjuvants are emulsions in oil of mineral or vegetable origin; mineral compounds such as aluminum phosphate or hydroxide, or calcium phosphate; bacterial products and derivatives, such as P40 (derived from the cell wall of Corynebacterium granulosum), monophosphoryl lipid A (MPL, derivative of LPS) and muramyl-peptide derivatives and conjugates thereof (derived from components of mycobacteria), alum, adjuvant of incomplete Freund, liposine, saponin, squalene, etc. Recent reviews of adjuvants for administration to humans are described by Gupta R.K. et al. (Vaccine 11, pages 293-306 (1993)) and by Johnson A.G. (Clin Microbiol Rev. 7, pages 277-289 (1994)). The pharmaceutical composition according to the present invention is prepared by the methods generally applied by the person skilled in the art for the preparation of various pharmaceutical compositions, especially vaccines, in which the proportion of pharmaceutically acceptable active compound / excipient can vary within very high margins. large (generally a suitable dosage unit form contains from about 0.005 μg to about 1 mg of the compound per kg of patient's body weight), limited only by the tolerance and level of patient acceptance to the compound. The limits are determined particularly by the frequency of administration and by the specific diseases and symptoms that are to be treated. Preferably, the compound is present in the pharmaceutical composition in a concentration that allows at least the reduction or suppression of the signs and symptoms of allergy or of a disease of allergic origin (preferably signs and symptoms of allergy of immediate hypersensitivity). The cosmetic composition according to the present invention can comprise any acceptable cosmetic excipient selected according to the specific mode of administration. For example, for skin hygiene, the cosmetic composition could consist of a product in the form of a cream, an ointment or a balm. The food or feed composition according to the present invention could be any acceptable excipient for food, feed or beverages comprising the normal components of liquids, foods or feeds in which the compound according to the invention is included. Another aspect of the present invention relates to the use of the compound according to the invention as a medicament. The present invention also relates to the use of the compound according to the invention or the pharmaceutical composition according to the invention for the preparation of a medicament for the prevention and / or treatment of allergy or of a disease of allergic origin, particularly allergy of immediate hypersensitivity Another aspect of the present invention relates to a method for the prevention and / or treatment of allergy or a disease of allergic origin, particularly the immediate hypersensitivity allergy, which comprises the step of administering the compound or pharmaceutical composition according to the invention. a patient, preferably a human patient, especially an atopic individual to an allergen, in order to advantageously give rise to or increase the production of antibodies towards antigenic determinants of the allergen that are not recognized spontaneously or are only minimally by the immune system of atopic individuals. These diseases include rhinitis and sinusitis of allergic origin, bronchial asthma, atopic dermatitis, some forms of acute and chronic urticaria, gastrointestinal syndromes associated with the ingestion of food allergens, such as β-lactoglobulin, the so-called oropharyngeal syndrome of the same origin and anaphylactic reactions associated with a hypersensitivity to drugs. The present invention will be described in the following examples, with reference to the attached figures. Said examples are presented as non-limiting illustrations of the various embodiments of the present invention.

BRIEF DESCRIPTION OF THE FIGURES Figure 1 depicts Balb / c mice immunized by two subcutaneous injections of rDer pll (10 μg in Freund's adjuvant) administered at a 2 week interval. Mice were bled and the reactivity of the antibodies was evaluated using a series of overlapping peptides covering the Der pll sequence or the T cell adjuvant (FIS). Mice recognizing peptide 11 (see item 2 of the Figure) were further immunized twice with 10 μg of peptide 21 and showed that they now recognized peptide 21 with a 50% reduction in antibody concentration for peptide 11. (point 3 of the Figure). An additional administration of rDer pll maintains the reactivity for peptide 21, while the concentration of antibodies for peptide 11 is further reduced (point 4). Figure 2 depicts a peptide labeled with biotin diluted in phosphate buffered saline, pH 7.4 (PBS) at a concentration of 2 μg / ml. Fifty μl of said dilution is added to plates coated with neutravidin and incubated for 1 hr at room temperature (RT). The plates are washed with PBS and the residual binding sites are saturated by the addition of 100 μl of casein diluted at 5 mg / ml in PBS. After 30 minutes at RT, the plate is washed again and incubated for 2 h at RT with a 1/5 dilution of serum from an atopic individual, washed again and incubated with goat antibodies specific for human IgE. they are coupled to peroxidase. After a further washing, the plate is incubated with a substrate for the enzyme which is colored after an enzymatic cleavage. The intensity of the staining in the wells (shown by absorbance at 490 nm on the Y axis) is proportional to the amount of specific IgE antibodies present in the serum sample. The control assays included dilution without peptides or without antibodies. Figure 3 represents an assay carried out as described in the explanation of Figure 2, except for the use of a 1/100 dilution of serum obtained from non-atopic subjects and the use of goat antibodies to human IgG. Figure 4 represents an assay carried out exactly as described for Figure 3, except in the use of serum obtained from atopic subjects. Figure 5 Twenty-five ml of blood is collected by venous puncture in a heparinized tube and diluted twice with RPMI medium and deposited on a Ficoll-Hypaque density gradient apparatus. The tubes are centrifuged for 20 min at 1,000 g. Interphase cells are collected by aspiration and resuspended in RPMI, washed twice with the same medium and finally resuspended in the same medium at a rate of 106 cells / ml. Fifty μl containing 10 μg / ml of either peptide 11-22 or 22-33 diluted in the medium is added for a 6-day incubation at a temperature of 37 ° C. A positive control with PHA (10 μg / ml) is added. The proliferation of T cells is determined by checking the degree of bromo-uridine incorporation (BrdU) in the DNA of the cells, using a specific antidust for BrdU. The results are shown in the absorbance at 490 nm. No proliferation of T cells above the base value can be observed with peptide 11-22.

DETAILED DESCRIPTION OF THE INVENTION Atopic as well as non-atopic subjects produce antibodies against environmental allergens. Said antibodies belong to all the isotypes that have been described to date, including IgE (Saint-Remy J.M.R. et al., J. Immunol., 43, pages 338-347 (1988)). It is usually observed that atopic individuals produce 10 to 100 times more anti-IgE than non-atopic individuals, which may explain at least partially the reason why atopic individuals suffer from symptoms when they encounter allergens. They are sensitized. It has been unexpectedly discovered that the antigenic determinants of allergens such as Der pl and Der pll - two of the main allergens of the domestic dust mite Dermatophagoides pteronyssinus - which are recognized by antichods of atopic individuals are not identical to those recognized by non-atopic individuals. This conclusion was reached using a series of monoclonal antibodies produced in mice against purified Der pl or Der pll molecules. In a competition immunoassay, the present inventors have determined that some of the antigenic determinants are recognized by anti-allergen antibodies from atopic individuals, while other determinants are recognized by anti-allergen antibodies produced by non-atopic individuals. In addition, they have shown that atopic patients whose allergic symptoms improved, either spontaneously or as a result of a treatment, began producing antibodies for the same determinants recognized by non-atopic individuals, while reducing the production of initial antibodies. The invention relates to the use of peptides derived from regions of allergen molecules that are recognized by antibodies produced by non-atopic individuals, or possibly from regions that do not produce a spontaneous antibody response. Administration of said peptides to atopic individuals results in the production of specific antibodies. These antibodies will bind allergens as long as patients are naturally exposed to them and, as a consequence, will restrict access of antibodies produced spontaneously by patients. Some atopic patients additionally produce a small proportion of antibodies to antigenic determinants recognized by non-atopic individuals. In such cases, an administration of said peptides will increase the proportion of said antibodies in order to make them predominant in the anti-allergen immune response. It is therefore the purpose of the present invention to provide a method by which the immune anti-allergen response is diverted towards epitopes that are not spontaneously recognized or are only minimally recognized by antibodies produced by atopic patients. The immunization method which is the subject of the present invention provides various advantages over other methods. Firstly, the immunization method according to the present invention is safe, since the peptides used do not carry determinants that can be recognized by anti-IgE antibodies and therefore have no ability to induce an anaphylactic reaction. Said property contrasts with administration procedures that utilize whole allergen molecules in their native or modified forms. Secondly, the amount of immunizing material and the number of injections required according to the invention are much smaller compared to alternative immunotherapeutic strategies, for the following reasons: (1) as the peptides produced by the present invention do not contain determinants that are When IgE binds, an immunogenic dose of peptide can be provided at once, which therefore appreciably shortens the time period of the treatment. A mixture or simultaneous administration of an adjuvant can increase the immunogenicity of the peptides, further reducing the number of injections (and the amount of material required) to possibly a single; (2) As atopic individuals can actually produce a small amount of antibodies directed to epitopes recognized by non-atopic individuals, an injection of peptides obtained by the present invention thus promotes a secondary immune response (a secondary immune response will result the production of antibody titers much higher than a primary immune response); (3) how the administration of peptides modifies the response To immunity to allergens at an early stage, ie the recognition of allergens, the processing by cells presenting antigens and the presentation to T cells, a limited amount of material will be all that is needed to achieve the objective of the present invention. . The characteristics described above represent a particular advantage over a conventional desensitization to be administered for several months or years and which makes use of a high amount of allergens. In alternative therapies, such as the use of peptides to confer energy to T cells, therapy requires much higher amounts of free peptides to compensate for the high rate of peptide catabolism, and repeated administration is required to maintain the energy status. Third, continued exposure to allergens present in the natural environment of patients treated by the present invention is sufficient to maintain the immune response towards the antigenic determinants corresponding to peptides used for immunization. There is actually available experimental evidence showing that mice immunized with a peptide derived from an antigen maintain their reactivity towards the peptide after a subsequent inoculation with the whole antigen (clonal dominance phenomenon) (Benjamini E. et al., J. Immunol., 141, pages 55-63 (1988) and Schutze MP et al., J. Immunol., 142, pages 2635-2640 (1989)) and attached figure 1). The method according to the present invention also represents a clear advantage over other therapies by which an allergen tolerance is sought instead of an immunization towards new antigenic determinants. In the first case, a repeated administration of tolerogens is required to maintain the state of lack of response capacity. The precise mode of action of the present invention is not yet fully elucidated. The number of possible antigenic determinants that can be recognized by antibodies in allergens is high. However, allergens are usually small molecules, which restricts the number of antibody molecules that can bind to allergens at the same time. Antibodies that are present at the highest concentration and / or which have the highest affinity will preferably bind to the allergen. The same is true for specific B cells, which express in their surface membrane an immunoglobulin molecule identical to the one they secrete. An antigen will therefore be captured by B cells that have the highest affinity and / or the highest frequency. This will prevent the activation of B cells that recognize other epitopes in the same molecule, a phenomenon that is called the "cloning dominance phenomenon" (Schutze MP et al., J. Immunol., 142, pages 2635-2640 (1989)). induces a preferential immune response in atopic individuals towards epitopes that are not recognized or only weakly by spontaneously formed antibodies, the phenomenon of clonal dominance indicates that the anti-allergen immune response will now be directed to these new determinants and reduced for antigenic determinants Initially, two lines of experimental evidence support this concept: Firstly, the elimination of an immunodominant B-cell epitope in an antigen reveals epitopes that were not recognized in the intact antigen and to which the response of the antigen is now directed. antibody (Scheerlinck JPY et al., Mol.Immunol 30 pages 733-739 (1993)). mice immunized with an antigen use only a fraction of their potential B cell repertoire to mount a specific immune response; Immunization with a peptide activates a selected repertoire of B cells, whose reactivity will be maintained even if the animal is later inoculated with the native antigen (Benjamini E. et al., J. Immunol. 141, pages 55-63 (1988)). Said two series of experiments illustrate what is happening as a consequence of the administration of the compound according to the present invention. As an additional support to the concept of clonal dominance and its application to allergy, Balb / c mice were injected with a recombinant allergen (r), Der pll. The precise specificity of the antibodies produced by said mice was determined by reaction with a panel of 15-mer peptides covering the entire Der pll sequence with an overlap of 5 amino acids. In the example shown in Figure 1, the mice are producing antibodies for rDer pll and for peptide 11-25. An additional immunization with peptide 21-35 induces an immune response to 21-35 and a significant reduction of binding to peptide 11-25. The immune response to Der pll therefore deviates towards determinants that were not recognized in the first place. In addition, said experiment shows that the "deviant" induced immune response resists additional immunization with the whole rDer pll allergen. To be fully effective, however, the peptide carrying a B cell epitope must be administered together with an epitope that can be recognized by T cells, which will provide the B cells with the signals necessary to allow a total differentiation in mature plasma cells, producers of antibodies. The T cell epitope does not have to be derived from the same molecule as the B cell. Therefore, a heteropéptype containing a B cell epitope derived from a given allergen and a T cell epitope from another source will maintain the specificity required at the level of the B cell, while ensuring that the necessary signals provided by T cells are present. These signals include the recognition of cognate BT cells and non-specific antigen signals, such as interleukin production, the interaction of CD40 with its ligand, the interaction of B7 (CD80) with CD28 (Austyn & amp; Wood, Principles of Cellular and Molecular Immunology, Oxford University Press (1993). The epitope (or epitopes) of T cells used for the present invention are selected according to their ability to activate T cells from most patients. Preferably, it is derived from an antigen normally used for a routine immunization, such as tetanus toxoid or diphtheria antigen. This comprises two main advantages. Firstly, a number of universal public T cell epitopes have been described in said molecules, that is, recognized by the vast majority of patients (Reece JC et al., J. Immunol. 151, pages 6175-6184 (1993 )). Second, since virtually all individuals are vaccinated against tetanus toxoid or diphtheria, priming with the T-cell epitope used for the present invention has already been achieved, which should increase the efficacy of vaccination, with a possible reduction of the doses and the number of injections. The peptides used for immunization in the context of the present invention are preferably produced by synthesis (see for example Grant Editions, Synthetic Peptides) by an applied biosystem peptide synthesizer model 430 A or 431 or by recombinant DNA techniques for their sequences nucleic acid encoders. The composition containing the peptides is in a form suitable for an injection subcutaneously, intramuscularly or intradermally. However, forms for inhalation, ingestion or direct application on the skin or mucosa are possible. The peptides may be in a linear or cyclic form, with or without additional residues used, for example, to block peptide-peptide interactions. The peptides can also be integrated into short peptide structures that force a specific 3-D conformation, such as an alpha helix. The composition may contain other material than peptides, such as adjuvants. The method described in the present invention can be used to treat diseases of humans or animals in which it has been demonstrated and considered that IgE antibodies play a role in the onset of symptoms. The present invention can also be applied to patients sensitive to allergens of animal or vegetable origin, or to chemical and pharmaceutical compounds, such as antibiotics (penicillin).

EXAMPLES EXAMPLE 1 A 31 amino acid peptide consisting of 15 AA representative of a tetanus toxoid T cell epitope (amino acids 830 to 844 of the heavy chain) and 14 AA containing an epitope of Der pll B cells, is obtained synthetically. two epitopes by a separator of two glycine residues. The sequence is SEQ ID No. 1 QYIKANSKFIGITELGGHEIKKVLVPGCHCS.

Characteristics of the peptide 1. The B cell epitope is not recognized by IgE antibodies The peptide is not recognized by IgE antibodies produced by individuals sensitive to the native protein. This is established by an immunoassay which is carried out as follows. The peptide is insolubilized on polystyrene microtiter plates and a panel of serum samples from Der pll-sensitive atopic individuals is added; the binding of specific IgE antibodies is detected by the addition of an isotype-specific reagent. In this way, a peptide (SEQ ID No. 2) of HEIKKVLVPGCHGS sequence corresponding to amino acids 11-24 of Der pll is obtained with a solid phase synthesis using procedures well known to those skilled in the art, with a remainder of Biotin added at its amino terminal end. The peptide is insolubilized on plates coated with neutravidin and allowed to react with the serum of an atopic individual. In Figure 2 the results of said experiment are shown. Thus, the serum of an atopic individual with IgE antibodies to Der pll was added to a plate coated with neutravidin which had been preincubated with 12-mer peptides covering the sequence 7-39 of Der pll with an overlap of 1 1 amino acids. No binding above the base value was observed for any of the 22 peptides, indicating the absence of IgE antibodies capable of binding to said sequences. 2. The B cell epitope is recognized by IqG antibodies from non-atopic individuals This was established using a test procedure similar to that described above for IgE antibodies, except that goat anti-human IgG antibodies were used for the detection of IgG antibodies and in that a 1/100 dilution of serum was used. In Figure 3 representative results of said experiment are provided, from which it can be observed that an important union takes place between amino acids 11 and 24, as well as between amino acids 22 and 34. The region 7-39 of Der pll contains thus, two binding sites for IgG from non-atopic individuals. 3. The T cell epitope is not recognized by IgG antibodies from atopic individuals This was established using a test procedure identical to the assay described above for non-atopic subjects, except that the serum is obtained in this case from patients who are hypersensitive to Der pll. The results shown in Figure 4 indicate that IgG from atopic individuals do not bind to the 11-24 region of Der pll. A minority of patients have antibodies that react with peptide 8-19. 4. The 11-24 region of Der pll does not contain a T cell epitope This was established by T cell proliferation assays using procedures well known to those skilled in the art (see for example, Current Protocols in Immunology, Coligan JE compilers, Kruisbeek AM, Margulies DH, Shevach EM and Strober W, Chapter 3, Greene Publishing Associates & John Wiley & Sons, 1992-1998). Peripheral blood mononuclear cells (PBMC) are separated from the whole blood by centrifugation with density gradient. The PBMC suspension is then incubated for 4 to 6 days, either with rDER pll or with a 12-mer peptide included in the 7-39 region of Der pll. The results shown in Figure 5 indicate that the addition of peptide 11-22 to the PBMC suspension did not result in T cell proliferation, whereas significant proliferation was observed with peptide 22-33 and with PHA, the latter being used as a positive control.

Use of the hybrid peptide The peptide (SEQ ID No. 1) is mixed with an adjuvant suitable for administration to humans in order to increase its immunogenicity. Thus, muramyl dipeptide (MDP) is used and is covalently coupled to the peptide according to published procedures (Matsumoto K et al., Immunostimulants: Now and Tomorrow, compilers I. Azuma and G. Jolles, pages 79-97 (1987). , Japan Sci. Soc. Press, Tokyo / Springer-Verlag, Berlin). The mixture containing the peptide and MDP is then administered to a Der pll-sensitive patient. Thus, a suspension containing 100 μg / ml of peptide is prepared in a saline solution containing 0.3% human serum albumin and 0.4% phenol. One ml of the solution is injected into the arm subcutaneously.

EXAMPLE 2 The compound of the present invention can be prepared by recombinant cDNA technology to produce a polypeptide consisting of a series of repeating peptide units containing T and B cell epitopes. A polypeptide consisting of an epitope of DNA is produced by DNA technology. duplicate T cells derived from TT (amino acids 830 to 844 of the heavy chain) and six repetitive B cell epitopes derived from Der pll. A sequence of two amino acid residues is inserted between each epitope. The sequence is: D - (QYIKANSKFIGITELX) 2 - (CHGSEPCIIHRGKPFX) 5 - CHGSEPCIIHRGKPFSR, wherein X is GG or SS. Said polypeptide is obtained as follows. The nucleotide sequence of the TT epitope corresponding to QYIKANSKFIGITEL (SEQ ID No. 13) and the epitope of Der pll 21-35 corresponding to CHGSEP-CIIHRGKPF (SEQ ID No. 14) are deduced. A theoretical assembly is made from nucleotides corresponding, on the one hand, to the TT-GG epitope TT epitope sequence (T subunit) and, on the other hand, to two copies of the Der pll epitope separated by a GG sequence. (subunit B). Oligonucleotides are synthesized that cover the complete sequence of each subunit (a subunit T and a subunit B). The complete DNA sequence encoding the two units is obtained by PCR. For the two TT subunits, the direct sense primer is: GTATCTCTCGAGAAAAGAGATCAATACATTAAGGCTAACAGTAAGTTCATT GG (SEQ ID No. 7); The antisense primer is: AAACAGCCTCTAGAGAGTTCGGTAATGCCGA- TAAACTTTGAATTGGCTTTGATGTACTGACCGCCAAGCTCTGTGATTCCAA TGAACTTACT-GTTAGCC (SEQ ID No. 8). For the two subunits B, the direct sense primer is: GTATCT- ACTAGTTGCCATGGTTCAGAACCATGTATCATTCATCGTGGTAAACCATTCGGCGGTTGT-CACGGAAGTGAGCCTTGCATTATACACAGAGGAAAGC (SEQ ID No. 9); and the antisense primer is: CGTATGTGTCGACCCGCTATCTAGAGAACGGCTTTCCTCTGTGTATA-ATGC (SEQ ID No. 10). The complete DNA sequence corresponding to the polypeptide is obtained by directional multimerization of subunits, using sequences flanked by restriction enzyme sites that generate compatible ends. The final 137 amino acid polypeptide sequence is: DQYIKANSKFIGITELGGQYIKANSKFIGITELSSCHGSEPCIIHRGKPFGGCHG SEPCIIHRGKPFSSCHGSEPCIIHRGKPFGGCHGSEPCIIHRGKPFSSCHGSEPCIIHRGKPFGGCHGSEPCIIH-RGKPFSR (SEQ ID NO: 3). The peptide CHGSEPCIIHRGKPF (SEQ ID No. 14) corresponding to the 21-35 amino acid sequence of Der pll does not contain an epitope that binds to IgE, as demonstrated in an assay similar to that described in Figure 2. It does, however, contain an epitope recognized by IgG antibodies from non-atopic individuals, but not from atopic subjects, as shown using assay systems similar to those described in Figure 3 and Figure 4, respectively. The 137 amino acid polypeptide is produced in yeast cultures using a methodology well known to those skilled in the art, and which can be found in reference texts, such as Current Protocole in Molecular Biology, Ausubel FM compilers, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA and Struhl K, chapter 16.13, John Wiley & Sons, 1994-1997. The polypeptide is applied by adsorption on aluminum hydroxide and is administered by subcutaneous injection at a dose of 100 μg. Two injections are given in a 3 week interval.

EXAMPLE 3 The nucleotide sequence encoding the compound of the present invention can be used for direct gene immunization. Said DNA-based vaccine can be delivered by different routes (i.e., intramuscular, intradermal, subcutaneous and oral) using "pure" DNA, encapsulated DNA or DNA in the form of micro- or nanoparticles such as chitosan (K. Roy et al. , Nature Medicine 1999; 5: 387-391). A nucleotide construct prepared as in Example 2, but containing the DNA sequence encoding a T cell epitope derived from TT and 2 epitopes from Der pll derived B cells, each epitope being separated by the GGAGGT or GGCGGT sequence encoding Two glycine residues, is used for a direct immunization by an intramuscular injection. The nucleotide sequence is flanked at 5 'by a sequence containing an EcoRI restriction site and a KOZAK sequence (ie, GAATTCCCACCATGG (SEQ ID No. 16)) and at 3' by a stop codon and a Notl restriction site. (ie TAGGCGGCCGC (SEQ ID No. 17)), and inserted into a suitable vector. The direct sense primer is: CCGGAATTCCCACCATGGATCAGTA- TATAAAAGCAAATTCTAAATTTATAGGTATAACTGAACTAGGAGGTTGCCAT GGTTCAG-AACCATGTATCATTCATCG (SEQ ID No. 11); and the antisense primer is: TCGAGCGGCCGCTTAGAACGGCTTTCCTCTGTGTATAATGCAAGGCTCAC TTCCGTGAAACCG- CCGAATGGTTTACCACGATGAATGATACATGGTTCTGAACC (SEQ ID NO: 12). The construction of the sequence GAATTCCCACCATGGATCAGTATATAAAA- GCAAATTCTAAATTTATAGGTATAACTGAACTAGGAGGTTGCCATGGTTCA GAACCATGTATCATTCATCGTGGTAAACCATTCGGCGGTTGTCACGGAAGTGAGCCTTGCATTATACACAGAGGAAAGCCGTTCTAAGCGGCCGC (SEQ ID No. 6) is used for the immunization of mice. Six Balb / c mice are primed with TT on day -7. On day 0, mice are anesthetized and intramuscular injections of 100 μg of DNA are given at two week intervals. The mice are bled after three injections and the serum is evaluated for the presence of antibodies to the T cell epitope produced from the DNA construct and to the full-length native Der pll molecule.

EXAMPLE 4 A peptide of 40 amino acids consisting of 13 AA representative of a T cell epitope of influenza A virus, a GKKG sequence corresponding to a canonical protease sensitive site, a repeated identical T cell epitope, a second is synthesized. GKKG and 6 AA that contain a B-cell epitope of Der pl. The sequence is PKYVKQNTLKLATGKKGPKYVKQNTLKLATGKKGVIIGIK (SEQ ID No. 4). The same characteristics as in Example 1 are demonstrated using similar test systems.

EXAMPLE 5 The wild-type sequence of the B-cell epitope-containing residue can be modified such that an intrinsic T-cell epitope is deleted while maintaining a complete immunogenicity of the B-determinant, thanks to the presence of another epitope of B-cell epitope. functional T cells within the immunizing peptide. In this way, a peptide with a length of 32 amino acids of sequence QYIKANSKFIGITELGGCHGSEPCNIHRGKPF (sequence ID n ° 5) is synthesized, as in Example 1. Said peptide corresponds to a T cell epitope derived from TT (amino acids 830 to 844 ) and a B cell epitope derived from Der pll, separated by a GG spacer. The B cell epitope sequence exhibits a point substitution at position 28, i.e., a substitution from I to N, which was shown to eliminate a major T cell epitope by assay systems, as described in Figure 5. The peptide is used for the immunization of mice. Thus, six Balb / c mice were injected in each leg with 50 μl of an emulsion containing 50 μg of the peptide in complete Freund's adjuvant. The same injection procedure is used twice in a two week interval, except for the use of incomplete Freund's adjuvant. Two weeks after the last injection, the mice were bled and the serum was shown to contain antibodies specific for the Der pll B cell epitope included in the synthetic peptide used for immunization, and for the full-length Der pll protein. Regional lymphatic drainage nodes are obtained for the preparation of a T cell suspension. It is shown that the latter proliferate in the presence of TT, but not in the presence of Der pll or the peptide corresponding to the rest of B cell used for immunization.

EXAMPLE 6 Multiple antigenic peptides can be used for an immunization with the advantage of increased immunogenicity and the possibility of using an immunogen containing B epitopes derived from different, possibly unrelated, allergen molecules. Multiple antigenic peptides, or branched peptides, are synthesized according to methods known to those skilled in the art. An appropriate description of the methodology can be found, for example, in Tam J. P., Proc. Nati Acad. Sci. USA 1988; 85: 5409-5413. A nuclear peptide consisting of 8 lysine residues (K) is prepared synthetically. Each group of epsilon-amine K can be replaced by a particular peptide attached to the K-backbone by a peptide bond. Therefore, the first 2 residues are replaced by the sequence QYIKANSKFIGITEL (SEQ ID No. 13) corresponding to the T cell epitope of TT (amino acids from 830 to 844). Residues 3 and 4 are substituted with the sequence CHGSEPCNIHRGKPF (SEQ ID NO: 14) which corresponds to the B cell epitope derived from Der pll with a I28N point substitution. Remains 5 and 6 are substituted with the sequence VIIGIK which contains a B cell epitope derived from Der pl, as shown in Example 4. Remains 7 and 8 are substituted with the sequence PKYVKONTLKLAT (SEQ ID No. 15) corresponding to a major T cell epitope of influenza A virus. The substituted branched peptide is used to immunize Balb / c mice by the same procedure as described in Example 5. It is shown that serum contains antibodies to Der proteins. pll and Der pl of full length and for the two T cell epitopes derived from these two allergens. A T cell proliferation assay shows a positive response to TT and the influenza A viral protein that contains the T cell epitope sequence.

EXAMPLE 7 The nucleotide sequence encoding the compound of the present invention can be administered by gene transfer technology using recombinant viral or non-viral vectors (eg, artificial lipid bilayers), molecular conjugates or modified recombinant organisms derived, for example, from salmonella or mycobacteria. Therefore, an adenoviral vehicle containing the same DNA sequence as in Example 3 is obtained by gene manipulation. Said vector is prepared from two components: an adenoviral DNA vector (Ad5 E1-E3-) and a cell line of encapsidation. The sequence encoding a T cell epitope and two B cell epitopes are first inserted into the plasmid pAd. The linearized chimeric plasmid is then co-transfected using standard DNA transfer techniques with the restricted Ad genome in 293 encapsidation cells that transcomplement E1 for homologous recombination in vivo. The viral strain prepared in 293 cells provides titers ranging from 3 x 10 to 2 x 10 plaque forming units per ml (pfu / ml). 107 pfu are administered by inhalation to Balb / c mice. The mice are bled three weeks later and the level of antibodies to Der pll and the rest of B cell contained in the immunizing construct are evaluated by means of a direct binding ELISA, as in Figure 3.

EXAMPLE 8 The human immunity of the compound of the present invention can be evaluated in a humanized animal model. For this purpose, mice with severe combined immunodeficiency (SCID) are reconstituted with immunocompetent cells of human origin. Peripheral blood mononuclear cells (PMBC, 15 x 106 per mouse) obtained from a Der pll-sensitive atopic donor are injected into the peritoneum of each mouse with SCID. Six mice reconstituted in such a manner are injected on days 1, 15 and 30, 50 μg of the recombinant polypeptide described in example 2. The mice are bled before and six weeks after the start of the immunization procedure. The serum is evaluated for the presence of antibodies to the recombinant polypeptide and is found to be negative before and positive after immunization using a direct binding assay similar to that described in Figure 4.

EXAMPLE 9 Cosmetic composition for skin hygiene The cosmetic composition according to the present invention can be used in cream form directly on the skin of the patient. The compounds according to the invention can also be incorporated into the oily phase instead of being dissolved in the aqueous phase.

EXAMPLE 10 Food composition (acidified milk whey) A whey was obtained which included the strain Lactobacillus and two strains of Streptococcus traditionally used for the production of yoghurt, from whey powder reconstituted to 12.5% in water. 40 I of said serum was pasteurized at a temperature of about 92 ° C for 6 min, homogenized at a temperature of about 75 ° C and a pressure of 150 bar (two levels) and cooled to a temperature of about 42 ° C . The milk whey to which the compound according to the invention had been incorporated (peptides of Examples 1 to 3) was incubated at a temperature of 42 ° C and a pH of about 5 and then cooled to a temperature of about 5 ° C. Said food composition according to the present invention is used directly by the patient by an oral administration.

LIST OF SEQUENCES < 110 > U.C.B. S.A. < 120 > COMPOSITE AND PROCEDURE FOR THE PREVENTION AND / OR TREATMENT OF ALLERGY < 130 > P.UCB.09 / WO < 140 > < 141 > < 160 > 17 < 170 > Patentln Ver. 2.1 < 210 > 1 < 211 > 31 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > 1 Gln Tyr laugh Lys Wing Aan Ser Lys? Hs lie Gly lie Tíir Glu Leu siy 1 5 10 15 Gly fí? S Glu II- Lys Lys Val Lau Val Pro Gly Cys His Gly? = R 20. zs 30 < 210 > 2 < 211 > 14 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > 2 His ei '.? lie Lys Lys Val Leu Val Pro Giy cys His Giy Se 1 5 10 < 210 > 3 < 211 > 137 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > 3 Asp Gln Tyr lie Lys Wing Asn Ser Lya Phe He Gly XÍ & Thr Giu Leu 1 5 - 10 13 Gly Gly Gln Tyr He Lys Wing Asa Being Lys Phe He Gly lia Thr Giu 20 25 30 i Leu Ssr Si Cys Kis Gly Ser Glu Pro Cys lia Xls His Arg Gly Lys 35? Q 45 Pro Phß Gly Giy Cys Eis Gly Ser Giu Pro Cys He lis Kis Arg Giy 50 55 60 Ly = Pro Phe Ssr Ser cys His Gly Ser Glu Pro Cys lie He His Arg 65 70 75 80 Gly Lys Pro? He Gly Gly Cys His Gly Ser Giu Pro cys He? Le His B5 90 35 Arg Gly Lys Pro Phe Ser Ser Cys His Gly Ser Glu Pro Cys lie iß 100 105 110 HiS. Arg Gly Lys Pro Phß Gly Gly Cys Ls Gly Sai Giu Pro Cys 115 120 125 He Kis Ar Gly Lys Pro Ph * Ser > . g 130 135 < 210 > 4 < 211 > 40 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > 4 Pro Lys Tyr Val Lys Gln Asn Thr Leu Lys Leu Wing Thr Gly Lys Lys i 5 10 15 Giy Pro Lys Tyr Val Ly = Gln Asn Thr Leu Lys Leu Wing Thr Gly Lys 20 25 30 Lys Gly Val lis lie Gly Ha Lys 35 40 < 210 > 5 < 211 > 32 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > 5 Gln Tyr He Lys Ala Asa Ser Lys Phß Ha sly He Thr Glu Lau Gly 1 5 10 15 Gly Cys Kis Giy Ser Glu Pro Cy3 ñ * n He His Arg Giy Lys? Ro Ph < s 20 22 30 < 210 > 6 < 21 1 > 175 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic nucleotide sequence < 400 > 6 gaattcccac catggarcag tititaaaag casattctaa attra.ta.g3t ata. = ctgaac SO taggaggttg cca ggttca gaaccatgta, tcattcatcg tggta = acra tccggcggtr 120 grcacggaag gagccttgc g: cacaca gagrgaaagc g t = t = ag = g gccgc 173 < 210 > 7 < 21 1 > 53 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: initiator < 400 > 7 gtatctc-tcg agaaaa aga tcaatacatt aaggctaaca gtaag cat tgg 53 < 210 > 8 < 211 > 99 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: initiator < 400 > 8 aaacagcctc tagagag tc ggcaatgccg ataaactctg aattggcttr gatgtactga 60 ccgccaagct: c-tgtgaxc.cc aargaactta ctgitagcc 99 < 210 > 9 < 211 > 103 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: initiator < 400 > 9 gtatcteacta gttgccatgg ttcagaacca tgtatcattc arcgtggtaa a. * i c gc SO ggtt fccacg gaagtgagcc tigcaütata cacagaggaa a e 103 < 210 > 10 < 211 > 51 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: initiator < 400 > 10 cgtatgtgtc gacccgccac ctagagaacg gctttcctcc gxgtacaatg c 51 < 210 > 11 < 211 > 103 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: initiator < 400 > eleven ccggaattcc caccatggat cagtatataa aagcaaattc taiatttata ggtataactg 50 aactaggagg ttgccatggt tcagaaccat gta ec rte a tcg -03 < 210 > 12 < 211 > 105 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: initiator < 400 > 12 tcgagcggcc gcttagaacg gctttcctct gtgtataatg caaggctcac ttccgtgaca 60 accgccgaac ggtttaccac gatgaatgac acatggttcc gaa.cc 105 < 210 > 13 < 211 > 15 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > 13 Glr. Tyr H-i Lya Ala. Asn Ser Ly = Phe He Giy He Th? Leu 1 5? O 15 < 210 > 14 < 211 > 15 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > 14 Cy = His Giy Ser Glu Pro Cys He He His Arg Gly Lys Pro Phe 1 5 10 15 < 210 > 15 < 211 > 11 < 212 > PRT < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: synthetic peptide < 400 > fifteen Thr .Ala Gly Gl .and Cys Gly Gly cys cys Gly cys i 5 10 < 210 > 16 < 211 > 15 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: KOZAK sequence < 400 > 16 15 gaattcccac catgg < 210 > 17 < 211 > 11 < 212 > DNA < 213 > Artificial sequence < 220 > < 223 > Description of the artificial sequence: sequence containing the stop codon and the restriction site Notl < 400 > 17 taggcggccg c 11

Claims (14)

1. NOVELTY OF THE INVENTION CLAIMS 1. - Compound for the prevention and / or treatment of allergy, which consists of at least one antigenic determinant of allergen that is recognized by a B cell or an antibody secreted by a B cell of a non-atopic individual to said allergen and by at least one antigenic determinant of an antigen different from said allergen that gives rise to the activation of T cells. 2.- Compound for the prevention and / or treatment of allergy, comprising a nucleotide sequence that encodes the two antigenic determinants of the The compound according to claim 1, said sequence possibly being linked to one or more active regulatory sequences in a patient's cell. 3. Compound according to claim 1 or 2, wherein said allergen antigenic determinant is not recognized by a T cell. 4. Compound according to any of claims 1 to 3, wherein the allergen is selected from the group consisting of: group consisting of the following main allergens: Derpl and Der pll of domestic dust mite Dermatophagoides pteronyssinus, the main antigen of Aspergillus fumigatus, staphylococcal enterotoxin B (SEB) and bovine β-lactoglobulin. 5. The compound according to any of claims 1 to 4, wherein the antigenic determinant of the antigen that gives rise to the activation of T cells is an epitope of. T cells of tetanus toxoid, diphtheria, mycobacteria or antigens of the influenza virus or measles. 6. The compound according to any of the preceding claims, wherein the antigenic determinant of the allergen and the antigenic determinant of the antigen consist of peptide sequences, preferably joined to each other, by means of a peptide linker. 7. Compound according to claim 6, wherein the linker is constituted by at least two amino acids. 8. Compound according to any of the preceding claims, characterized in that the compound is selected from the group consisting of the peptides having the following amino acid sequences: SEC ID n ° 1: QYIKANSKFIGITELGGHEIKKVLVPGCHGS SEQ ID No 3: DQYIKANSKFIGITELGGQYIKANSKFIGITELSSCHGSEPCIIHRGKPFGGCHG SEPCIIHRGKPFSSCHGSEPCIIHRGKPFGGCHGSEPCIIHRGKPFSSCHGSE PCIIHRGKPFGGCHGSEPCIIHRGKPFSR SEQ ID No 4: PKYVKQNTLKLATGKKGPKYVKQNTLKLATGKKGVIIGIK SEQ ID No 5: QYIKANSKFIGITELGGCHGSEPCNIHRGKPF or a nucleotide sequence encoding at least one of said amino acid sequences, preferably the sequence SEQ ID No 6: GAATTCCCACCATGGATCA-GTATATAAAAG- CAAATTCTAAATTTATAGGTATAACTGAACTAGGAGGTTGCCATGGTT-CAGAACCATGTATCATTCATCGTGGTAAAC- CATTCGGCGGTTGTCACGGAAGTGAGC-CTTGCATTATACACAGAGGA-AAGCCGTTCTAAGCGGCCGC. 9. Pharmaceutical composition comprising the compound according to any of the preceding claims and a pharmaceutically acceptable excipient. 10. Cosmetic composition comprising the compound according to any of claims 1 to 8 and an acceptable cosmetic excipient. 11. Composition of beverage, food and / or feed comprising the compound according to any of claims 1 to 8 and an acceptable excipient for liquids, food and / or feed. 12. Compound according to any of claims 1 to 8, for use as a medicine. 13. - Use of the compound according to any of claims 1 to 8 or the pharmaceutical composition according to claim 9, for the preparation of a medicament for the prevention and / or treatment of allergy or a disease of allergic origin, particularly allergy of immediate hypersensitivity 14. Use according to claim 13, wherein the disease is selected from the group consisting of rhinitis and sinusitis of allergic origin, bronchial asthma, atopic dermatitis, some form of acute and chronic urticaria, gastrointestinal syndromes associated with ingestion of food allergens, the so-called oropharyngeal syndrome of the same origin, anaphylactic reactions associated with hypersensitivity to drugs and / or mixtures thereof.